Characterization of IL-2 Stimulation and TRPM7 Pharmacomodulation in NK Cell Cytotoxicity and Channel Co-Localization with PIP<sub>2</sub> in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex multisystemic disorder responsible for significant disability. Although a unifying etiology for ME/CFS is uncertain, impaired natural killer (NK) cell cytotoxicity represents a consistent and measurable feature of this disorder...

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Main Authors:	Stanley Du Preez, Natalie Eaton-Fitch, Helene Cabanas, Donald Staines, Sonya Marshall-Gradisnik
Format:	article
Language:	EN
Published:	MDPI AG 2021
Subjects:	myalgic encephalomyelitis chronic fatigue syndrome natural killer cell transient receptor potential melastatin 7 IL-2 PIP<sub>2</sub> Medicine R
Online Access:	https://doaj.org/article/7fe6383a99104545980c7c98bdd6acda
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spelling	oai:doaj.org-article:7fe6383a99104545980c7c98bdd6acda2021-11-25T17:49:09ZCharacterization of IL-2 Stimulation and TRPM7 Pharmacomodulation in NK Cell Cytotoxicity and Channel Co-Localization with PIP<sub>2</sub> in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients10.3390/ijerph1822118791660-46011661-7827https://doaj.org/article/7fe6383a99104545980c7c98bdd6acda2021-11-01T00:00:00Zhttps://www.mdpi.com/1660-4601/18/22/11879https://doaj.org/toc/1661-7827https://doaj.org/toc/1660-4601Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex multisystemic disorder responsible for significant disability. Although a unifying etiology for ME/CFS is uncertain, impaired natural killer (NK) cell cytotoxicity represents a consistent and measurable feature of this disorder. Research utilizing patient-derived NK cells has implicated dysregulated calcium (Ca<sup>2+</sup>) signaling, dysfunction of the phosphatidylinositol-4,5-bisphosphate (PIP<sub>2</sub>)-dependent cation channel, transient receptor potential melastatin (TRPM) 3, as well as altered surface expression patterns of TRPM3 and TRPM2 in the pathophysiology of ME/CFS. TRPM7 is a related channel that is modulated by PIP<sub>2</sub> and participates in Ca<sup>2+</sup> signaling. Though TRPM7 is expressed on NK cells, the role of TRPM7 with IL-2 and intracellular signaling mechanisms in the NK cells of ME/CFS patients is unknown. This study examined the effect of IL-2 stimulation and TRPM7 pharmacomodulation on NK cell cytotoxicity using flow cytometric assays as well as co-localization of TRPM7 with PIP<sub>2</sub> and cortical actin using confocal microscopy in 17 ME/CFS patients and 17 age- and sex-matched healthy controls. The outcomes of this investigation are preliminary and indicate that crosstalk between IL-2 and TRMP7 exists. A larger sample size to confirm these findings and characterization of TRPM7 in ME/CFS using other experimental modalities are warranted.Stanley Du PreezNatalie Eaton-FitchHelene CabanasDonald StainesSonya Marshall-GradisnikMDPI AGarticlemyalgic encephalomyelitischronic fatigue syndromenatural killer celltransient receptor potential melastatin 7IL-2PIP<sub>2</sub>MedicineRENInternational Journal of Environmental Research and Public Health, Vol 18, Iss 11879, p 11879 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	myalgic encephalomyelitis chronic fatigue syndrome natural killer cell transient receptor potential melastatin 7 IL-2 PIP<sub>2</sub> Medicine R
spellingShingle	myalgic encephalomyelitis chronic fatigue syndrome natural killer cell transient receptor potential melastatin 7 IL-2 PIP<sub>2</sub> Medicine R Stanley Du Preez Natalie Eaton-Fitch Helene Cabanas Donald Staines Sonya Marshall-Gradisnik Characterization of IL-2 Stimulation and TRPM7 Pharmacomodulation in NK Cell Cytotoxicity and Channel Co-Localization with PIP<sub>2</sub> in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients
description	Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex multisystemic disorder responsible for significant disability. Although a unifying etiology for ME/CFS is uncertain, impaired natural killer (NK) cell cytotoxicity represents a consistent and measurable feature of this disorder. Research utilizing patient-derived NK cells has implicated dysregulated calcium (Ca<sup>2+</sup>) signaling, dysfunction of the phosphatidylinositol-4,5-bisphosphate (PIP<sub>2</sub>)-dependent cation channel, transient receptor potential melastatin (TRPM) 3, as well as altered surface expression patterns of TRPM3 and TRPM2 in the pathophysiology of ME/CFS. TRPM7 is a related channel that is modulated by PIP<sub>2</sub> and participates in Ca<sup>2+</sup> signaling. Though TRPM7 is expressed on NK cells, the role of TRPM7 with IL-2 and intracellular signaling mechanisms in the NK cells of ME/CFS patients is unknown. This study examined the effect of IL-2 stimulation and TRPM7 pharmacomodulation on NK cell cytotoxicity using flow cytometric assays as well as co-localization of TRPM7 with PIP<sub>2</sub> and cortical actin using confocal microscopy in 17 ME/CFS patients and 17 age- and sex-matched healthy controls. The outcomes of this investigation are preliminary and indicate that crosstalk between IL-2 and TRMP7 exists. A larger sample size to confirm these findings and characterization of TRPM7 in ME/CFS using other experimental modalities are warranted.
format	article
author	Stanley Du Preez Natalie Eaton-Fitch Helene Cabanas Donald Staines Sonya Marshall-Gradisnik
author_facet	Stanley Du Preez Natalie Eaton-Fitch Helene Cabanas Donald Staines Sonya Marshall-Gradisnik
author_sort	Stanley Du Preez
title	Characterization of IL-2 Stimulation and TRPM7 Pharmacomodulation in NK Cell Cytotoxicity and Channel Co-Localization with PIP<sub>2</sub> in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients
title_short	Characterization of IL-2 Stimulation and TRPM7 Pharmacomodulation in NK Cell Cytotoxicity and Channel Co-Localization with PIP<sub>2</sub> in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients
title_full	Characterization of IL-2 Stimulation and TRPM7 Pharmacomodulation in NK Cell Cytotoxicity and Channel Co-Localization with PIP<sub>2</sub> in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients
title_fullStr	Characterization of IL-2 Stimulation and TRPM7 Pharmacomodulation in NK Cell Cytotoxicity and Channel Co-Localization with PIP<sub>2</sub> in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients
title_full_unstemmed	Characterization of IL-2 Stimulation and TRPM7 Pharmacomodulation in NK Cell Cytotoxicity and Channel Co-Localization with PIP<sub>2</sub> in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients
title_sort	characterization of il-2 stimulation and trpm7 pharmacomodulation in nk cell cytotoxicity and channel co-localization with pip<sub>2</sub> in myalgic encephalomyelitis/chronic fatigue syndrome patients
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/7fe6383a99104545980c7c98bdd6acda
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_version_	1718411995098644480

Characterization of IL-2 Stimulation and TRPM7 Pharmacomodulation in NK Cell Cytotoxicity and Channel Co-Localization with PIP<sub>2</sub> in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients

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